The Role of Interleukin-6/GP130 Cytokines in Cancer Cachexia

Cancer cachexia is characterized by the involuntary loss of skeletal muscle with or without adipose tissue loss in the presence of tumor burden. It is a prevalent yet clinically unmet need that results in devastating systemic wasting effects. Chronic inflammation triggers cancer progression and is observed in cachexia. This review will highlight the Interleukin-6 (IL-6) family of cytokines, including IL-6 itself, Leukemia Inhibitory Factor (LIF), Ciliary Neurotrophic Factor (CNTF), Cardiotrophin-1 (CT-1), Oncostatin M (OSM), Interleukin-11 (IL-11), Interleukin-27 (IL-27), and Cardiotrophin-like cytokine (CLC), which all share signaling through IL-6 Signal Transducer (IL6ST), also known as Glycoprotein 130 (GP130) to activate common downstream pathways including the JAK/STAT, MAPK, and AKT pathways. IL-6 has been long linked to cancer cachexia through both associative and functional studies; furthermore, anti-IL-6 therapies have been trialed in patients. Recently, LIF has emerged as a novel cachexia mediator in experimental systems. Far less is known about the other cytokines in cachexia, although they have suggestive properties on adipose and muscle tissues in other contexts. Future studies are required to determine the roles of these other factors in cancer cachexia and their potential for designing therapies.